Alcohol impairs the immune system and increases susceptibility to infection. B-lymphocyte number and function is depleted with acute and short term exposure to alcohol. This proposal is designed to test the hypothesis that long term chronic alcohol exposure first causes a decreased in surface expression of MHC class II and immunoglobulin on B- cells, leading to decreases in B-cell numbers and their response to specific antigens. Aim 1 is to determine by flow cytometry B-cell surface expression of immunoglobulin and MHC class of mice exposed to long term chronic alcohol. mRNA levels of MHC class I and immunoglobulin will be measured by RT-PCR to determine if decreases occur at the transcriptional level. Mice will be immunized with sheep red blood cells and number of antibody producing cells quantitated by Jerne plaque assay. Aim 2 is to determine the effect of long term alcohol exposure on B-cells in monkeys, and then to examine that effect in the context of SIV infection. B-cells will be counted, and surface MHC class II and immunoglobulin expression will be measured using flow cytometry. SIV-specific antibodies will be measured by elisa and by neutralizing antibody assays. We expect to find that long term alcohol exposure causes a series of B-cell defects, beginning with decreased MHC class II expression and ultimately resulting in decreased B-cell numbers in the spleen and the peripheral blood. This work will lay the foundation for later studies to determine the mechanism for alcohol induced humoral immunodeficiency.